Scope:High-fat diet(HFD)induces imbalance in the small intestine environment,where fat digestion and absorption mainly take place.This study aimed to elucidate the mechanisms by which Lonicera caerulea polyphenols(LCP...Scope:High-fat diet(HFD)induces imbalance in the small intestine environment,where fat digestion and absorption mainly take place.This study aimed to elucidate the mechanisms by which Lonicera caerulea polyphenols(LCP)might inhibit fat absorption,from the perspective of small intestine microbiota and epithelial barrier integrity.Methods and results:Male Sprague-Dawley rats were given HFD with or without co-administration of LCP for 8 weeks.The results showed that LCP supplementation significantly decreased the levels of serum triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C),and increased the contents of fecal sterols,in HFD rats.LCP also inhibited the dysfunction of the small intestine epithelial barrier,via alleviating the oxidative stress activated by Nrf2-ARE pathway,and by modulating the expressions of pro-inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),cyclooxygenase-2(COX-2),nuclear factor kappa-B p65(NF-κB p65)and inducible nitric oxide synthase(iNOS)in the small intestine.Additionally,LCP administration restored the balance in small intestine microbiota and increased the abundance of the specific bacteria,such as Lactobacillus,involved in fat absorption.Conclusion:Our results demonstrated that LCP may be beneficial to inhibit fat absorption.The mechanism seems to be associated with the protection of the epithelial barrier integrity and the modulation of specific bacteria in the small intestine.展开更多
The plausibility of human exposure to particulate matter(PM)has witnessed an increase within the last several years.PM of different sizes has been discovered in the atmosphere given the role of dust transport in weath...The plausibility of human exposure to particulate matter(PM)has witnessed an increase within the last several years.PM of different sizes has been discovered in the atmosphere given the role of dust transport in weather and climate composition.As a regulator,the lung epithelium orchestrates the innate response to local damage.Herein,we developed a lung epithelium-ona-chip platform consisting of easily moldable polydimethylsiloxane layers along with a thin,flexible,and transparent ionic liquid-based poly(hydroxyethyl)methacrylate gel membrane.The epithelium was formed through the culture of human lung epithelial cells(Calu-3)on this membrane.The mechanical stress at the air–liquid interface during inhalation/exhalation was recapitulated using an Arduino-based servo motor system,which applied a uniaxial tensile strength from the two sides of the chip with 10%strain and a frequency of 0.2 Hz.Subsequently,the administration of silica nanoparticles(PM0.5)with an average size of 463 nm to the on-chip platform under static,dynamic,and dynamic+mechanical stress(DMS)conditions demonstrated the effect of environmental pollutants on lung epithelium.The viability and release of lactate dehydrogenase were determined along with proinflammatory response through the quantification of tumor necrosis factor-α,which indicated alterations in the epithelium.展开更多
AIM: To investigate the effects of moxibustion on down-regulation of the colonic epithelial cell apoptosis and repair of the tight junctions in rats with Crohn's disease (CD). METHODS: Sixty male Sprague-Dawley ra...AIM: To investigate the effects of moxibustion on down-regulation of the colonic epithelial cell apoptosis and repair of the tight junctions in rats with Crohn's disease (CD). METHODS: Sixty male Sprague-Dawley rats were randomly divided into a normal control (NC) group, a model control (MC) group, an herbs-partitioned moxibustion (HPM) group, a mild-warm moxibustion (MWM) group and a salicylazosulphapyridine (SASP) group, with 12 rats in each group. The CD model rats were treated with trinitrobenzene sulphonic acid to induce intestinal inflammation. The rats in the HPM and MWM groups were treated at the Tianshu (ST25) and Qihai (CV6) acupoints once daily for 14 d, and the SASP group was fed SASP twice daily for 14 d. No additional treatment was given to the MC and NC groups. Themicrostructure of the colonic epithelium was observed under a transmission electron microscope, the transepithelial resistance was measured using a shortcircuit current, colonic epithelial cell apoptosis was determined by terminal deoxynucleotidyl transferasemediated dUTP-biotin nick end labelling assay, and the expression of occludin, claudin-1 and zonula occludens-l (ZO-1) in the colonic epithelial junction was determined by Western blotting and immunofluorescence staining. RESULTS: Compared with the MC group, the microstructure of the colonic epithelial barrier was signifi-cantly improved in rats treated with HPM, MWM or SASP, meanwhile, the current flow was reduced signifi-cantly, with values of 168.20 ± 6.14 vs 99.70 ± 3.13, 99.10 ± 4.28 and 120.30 ± 3.65 mA, respectively (P = 0.001). However, the HPM and MWM groups had higher current flow rates than the SASP group (99.70 ± 3.13, 99.10 ± 4.28 vs 120.30 ± 3.65 mA, P = 0.001). The number of the apoptotic colonic epithelial cells in HPM, MWM and SASP groups was largely reduced (61.5 ± 16.91 vs 15.5 ± 8.89, 14.8 ± 6.27 and 24.7 ± 9.68, respectively (P = 0.001); and the expression of occlu- din, claudin-1 and ZO-1 in the MWM and HPM groups was signifi cantly enhanced (0.48 ± 0.10, 0.64 ± 0.09 vs 0.18 ± 0.05 for occludin, 0.12 ± 0.02, 0.17 ± 0.03 vs 0.05 ± 0.01 for claudin-1, and 0.08 ± 0.01, 0.11 ± 0.01 vs 0.02 ± 0.01 for ZO-1). And in SASP group, the expression of occludin and ZO-1 was also signifi cantly increased (0.27 ± 0.04 vs 0.18 ± 0.05 for occludin and 0.05 ± 0.01 vs 0.02 ± 0.01 for ZO-1), but there was no significant difference for claudin-1. The HPM and MWM groups had higher expression of occludin, claudin-1 and ZO-1 than the SASP group. CONCLUSION: HPM and MWM treatment can down-regulate apoptosis of colonic epithelial cells, repair tight junctions and enhance colonic epithelial barrier function in rats with CD.展开更多
Irritable bowel syndrome(IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to...Irritable bowel syndrome(IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to contribute to the genesis of symptoms in IBS, a search for an underlying aetiology has, to date, proven unsuccessful. Recently, attention has been focused on the microbiota as a possible factor in the pathogenesis of IBS. Prompted by a number of clinical observations, such as the recognition of the de novo development of IBS following enteric infections, as well as descriptions of changes in colonic bacterial populations in IBS and supported by clinical responses to interventions, such as antibiotics and probiotics, that modify the microbiota, various approaches have been taken to investigating the microbiota-host response in IBS, as well as in animal models thereof. From such studies a considerable body of evidence has accumulated to indicate the activation or upregulation of both factors involved in bacterial engagement with the host as well host defence mechanisms against bacteria. Alterations in gut barrier function, occurring in response, or in parallel, to changes in the microbiota, have also been widely described and can be seen to play a pivotal role in generating and sustaining host immune responses both within and beyond the gut. In this manner a plausible hypothesis, based on an altered microbiota and/or an aberrant host response, for the pathogenesis, of at least some instances of IBS, can be generated.展开更多
AIM： To determine whether Lactobacillus plantarum can modify the deleterious effects of tumor necrosis factor-α （TNF-α） on intestinal epithelial cells. METHODS： Caco-2 cells were incubated with TNF-α alone or i...AIM： To determine whether Lactobacillus plantarum can modify the deleterious effects of tumor necrosis factor-α （TNF-α） on intestinal epithelial cells. METHODS： Caco-2 cells were incubated with TNF-α alone or in the presence of L. plantarum. Transepithelial electrical resistance was used to measure epithelial barrier function. Interleukin 8 （IL-8） secretion by intestinal epithelial cells was measured using an ELISA. Cellular lysate proteins were immunoblotted using the anti-extracellular regulated kinase （ERK）, anti-phospho- ERK and anti-IκB-α. RESULTS： A TNF-α-induced decrease in transepithelial electrical resistance was inhibited by L. plantarum. TNF- α-induced IL-8 secretion was reduced by L. plantarum. L. plantarum inhibited the activation of ERK and the degradation of IκB-α in TNF-a-treated Caco-2 cells. CONCLUSION： Induction of epithelial barrier dysfunction and IL-8 secretion by TNF-α is inhibited byL. plantarum. Probiotics may preserve epithelial barrier function and inhibit the inflammatory response by altering the signal transduction pathway.展开更多
AIM: To investigate the effect of emodin on expression of claudin4, claudin5 and occludin, as well as the alveolar epithelial barrier in rats with pancreatitis induced by sodium taurocholate. METHODS: Experimental pan...AIM: To investigate the effect of emodin on expression of claudin4, claudin5 and occludin, as well as the alveolar epithelial barrier in rats with pancreatitis induced by sodium taurocholate. METHODS: Experimental pancreatitis was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Emodin was injected via the external jugular vein 3 h after induction of acute pancreatitis. Rats from sham operation group and acute pancreatitis group were injected with normal saline (an equivalent volume as emodin) at the same time point. Samples of lung and serum were obtained 6 h after drug administration. Pulmonary morphology was examined with HE staining. Pulmonary edema was estimated by measuring water content in lung tissue samples. Tumor necrosis factorα (TNFα) and interleukin6 (IL6) level were measured by enzymelinked immunospecific assay. Serum amylase and pulmonary myeloperoxidase (MPO) activity were detected by spectrophotometry. Alveolar epithelial barrier was assessed by pulmonary dye extravasation. Expression of claudin4, claudin5 and occludin in lung tissue samples was examined by immunohistology, quantitative realtime reverse transcription polymerase chain reaction and Western blotting analysis, respectively.RESULTS: Pancreatitis-associated lung injury was char-acterized by pulmonary edema, leukocyte infiltration, alveolar collapse, and elevated serum amylase level. The pulmonary damage, pulmonary pathological scores, serum amylase and MPO activity, TNF-α and IL-6 levels, and wet/dry ratio were decreased in rats after treatment with emodin. Immunostaining of claudin-4, claudin-5 and occludin was detected in lung tissue samples from rats in sham operation group, which was distributed in alveolar epithelium, vascular endothelium, and bron-chial epithelium, respectively. The mRNA and protein expression levels of claudin-4, claudin-5 and occludin in lung tissue samples were markedly decreased, the expression level of claudin-4, claudin-5 and occluding was increased, and the pulmonary dye extravasation was reduced in lung tissue samples from rats with acute pancreatitis after treatment with emodin.CONCLUSION: Emodin attenuates pulmonary edema and inflammation, enhances alveolar epithelial barrier function, and promotes expression of claudin-4, claudin-5 and occludin in lung tissue samples from rats with acute pancreatitis.展开更多
The pathogenesis of inflammatory bowel diseases (IBDs) seems to involve a primary defect in one or more of the elements responsible for the maintenance of intestinal homeostasis and oral tolerance. The most important ...The pathogenesis of inflammatory bowel diseases (IBDs) seems to involve a primary defect in one or more of the elements responsible for the maintenance of intestinal homeostasis and oral tolerance. The most important element is represented by the intestinal barrier, a complex system formed mostly by intestinal epithelial cells (IECs). IECs have an active role in producing mucus and regulating its composition; they provide a physical barrier capable of controlling antigen traff ic through the intestinal mucosa. At the same time, they are able to play the role of non-professional antigen presenting cells, by processing and presenting antigens directly to the cells of the intestinal immune system. On the other hand, immune cells regulate epithelial growth and differentiation, producing a continuous bi-directional cross-talk within the barrier. Several alterations of the barrier function have been identif ied in IBD, starting from mucus features up to its components, from epithelial junctions up to the Toll-like receptors, and altered immune responses. It remains to be understood whether these defects are primary causes of epithelial damage or secondary effects. We review the possible role of the epithelial barrier and particularly describe the role of IECs in the pathogenesis of IBD.展开更多
AIM To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis. METHODS Thirty C57BL/6 mice were given either regular drinkin...AIM To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis. METHODS Thirty C57BL/6 mice were given either regular drinking water (control group) or 2% (w/v) DSS drinking water (model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 mu g/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-a (TNF-alpha), interleukin 17 (IL-17) and interferon-. (IFN-gamma). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeled-dextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction (TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The mRNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-qPCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-alpha, IL-17 and IFN-gamma. CONCLUSION Our study suggested that poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses, which may shed light on the therapeutic potential of poly I:C in human colitis.展开更多
Objective:To investigate the effect of Gracilaria fisheri oligosaccharides(GFO)on inflammation and colonic epithelial barrier dysfunction in colitis mice.Methods:The animals were treated by oral gavage with distilled ...Objective:To investigate the effect of Gracilaria fisheri oligosaccharides(GFO)on inflammation and colonic epithelial barrier dysfunction in colitis mice.Methods:The animals were treated by oral gavage with distilled water,1000 mg/kg inulin,100,500,or 1000 mg/kg GFO for 14 d,or treated with 50 mg/kg mesalamine for 5 d after colitis induction(on day 10).Histopathology,inflammatory cytokines,colonic permeability,and tight junction proteins were investigated by hematoxylin and eosin staining,immunohistochemical staining,Ussing chamber technique,and Western blotting assays,respectively.Results:GFO ameliorated histological damage in colitis mice when compared to untreated colitis mice.Treatments with 100,500,and 1000 mg/kg GFO reduced TNF-αexpression,while IL-1βwas significantly reduced in colitis mice treated with 500 and 1000 mg/kg.Compared to untreated colitis mice,GFO increased transepithelial electrical resistance,reduced fluorescein isothiocyanate-dextran paracellular flux,and modulated tight junction proteins(occludin and claudin 2)in colitis mice.Conclusions:GFO has anti-inflammatory activity and could modulate colonic epithelial barrier dysfunction in acetic acid-induced colitis mice.Furthermore,GFO could modulate the expression of tight junction proteins that play important roles in colonic barrier function.展开更多
Pogostemon cablin essential oil(PEO),extracted from P.cablin,has anti-oxidant,anti-inflammatory,and anti-stress properties,as well as the ability to improve gastrointestinal digestion.This study aims to evaluate the e...Pogostemon cablin essential oil(PEO),extracted from P.cablin,has anti-oxidant,anti-inflammatory,and anti-stress properties,as well as the ability to improve gastrointestinal digestion.This study aims to evaluate the effects of PEO on the performance,rumen epithelial morphology,and barrier function in heat-stressed beef cattle.Thirty-six male Jingjiang cattle at 18 months old were randomly assigned into four groups and fed a diet containing PEO at 0(control),50,100,or 150 mg/kg in the feed concentrate(n=9).All experimental cattle were fed under high temperature and humidity in summer for 60 days.The results indicated that 50 mg/kg of PEO treatment enhanced the average daily gain of beef cattle compared with the control group(P=0.032).All PEO treatments reduced the diamine oxidase activity(P=0.004)and malondialdehyde content(P=0.008)in serum.In addition,the content of 70 kDa heat shock protein in the 100 mg/kg group was increased,and the activity of glutathione peroxidase and total antioxidant capacity in both 100 mg/kg and 150 mg/kg groups were enhanced compared to the control group(P<0.05).More importantly,PEO treatment with 50 mg/kg enhanced the mRNA relative expressions of occludin in ruminal epithelia but decreased the mRNA relative expressions of c-Jun N-terminal kinase,P38 mitogen-activated protein kinases,caspase-3,Beclin1(P<0.05),and extremely significant declined the mRNA relative expressions of extracellular regulated protein kinases and ubiquitin-binding protein in contrast to the control group(P<0.01).These findings indicated that dietary PEO supplementation might be favorable to improve growth performance and repairing damaged rumen epithelium of heat-stressed cattle by down-regulating the mitogen-activated protein kinase signaling pathway.展开更多
Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier function.Short-chain fatty acids (SCFAs),as metabolites of the gut microbiota,protect the physiological intestinal barrier;h...Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier function.Short-chain fatty acids (SCFAs),as metabolites of the gut microbiota,protect the physiological intestinal barrier;however,they are compromised when VA is deficient.Thus,there is an urgent need to understand how and which SCFAs modulate colonic epithelial barrier integrity in VA deficiency (VAD).Herein,compared with normal VA rats (VAN),at the beginning of pregnancy,we confirmed that the colonic desmosome junction was impaired in the VAD group,and the amounts of acetate,propionate,and butyrate declined because of the decreased abundance of SCFA-producing bacteria (Romboutsia ,Collinsella ,and Allobaculum ).The differentially expressed genes correlated with the gut barrier and the histone deacetylase complex between the VAD and VAN groups were enriched by RNA sequencing.In the VAD group,the expression levels of colonic CEA cell adhesion molecule 1 (CEACAM1) were down-regulated,and the levels of histone deacetylase 1 (HDAC1) and HDAC3 were up-regulated.Intriguingly,the above changes in the VAD groups were rescued by VA supplementation in the early postnatal period.Further study indicated that in Caco-2 cells,butyrate treatment significantly repressed the enrichment of HDAC3 on the promoter of the CEACAM1 gene to induce its expression.Our findings support that butyrate intervention can alleviate the impairment of colonic barrier function caused by VAD,and timely postnatal VA intervention may reverse the damage caused by VAD on gut barrier integrity during pregnancy.展开更多
Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are inter...Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are interdependent and establish a complex interaction network that restricts each other.According to the impact on the human body,there are three categories of symbiotic bacteria,opportunistic pathogens,and pathogenic bacteria.The intestinal microecology participates in digestion and absorption,and material metabolism,and inhibits the growth of pathogenic microorganisms.It also acts as the body’s natural immune barrier,regulates the innate immunity of the intestine,controls the mucosal barrier function,and also participates in the intestinal epithelial cells’physiological activities such as hyperplasia or apoptosis.When the steady-state balance of the intestinal microecology is disturbed,the existing core intestinal microbiota network changes and leads to obesity,diabetes,and many other diseases,especially irritable bowel syndrome,inflammatory bowel disease(IBD),and colorectal malignancy.Intestinal diseases,including tumors,are particularly closely related to intestinal microecology.This article systematically discusses the research progress on the relationship between IBD and intestinal microecology from the pathogenesis,treatment methods of IBD,and the changes in intestinal microbiota.展开更多
AIM: To investigate the effect of the probiotic combination Lactibiane Tolerance<sup>®</sup> (LT) on epithelial barrier function in vitro and in vivo.
Polyphenols,including phenolic acids,flavonoids,and procyanidins,are abundant in food and beverage derived from plants.Tea(Camellia sinensis)is particularly rich in polyphenols(e.g.,catechins,theaflavins,thearubigins,...Polyphenols,including phenolic acids,flavonoids,and procyanidins,are abundant in food and beverage derived from plants.Tea(Camellia sinensis)is particularly rich in polyphenols(e.g.,catechins,theaflavins,thearubigins,gallic acid,and flavonols),which are thought to contribute to the health benefits of tea.High intake of tea polyphenols has been described to prevent and/or attenuate a variety of chronic pathological conditions like cardiovascular diseases,neurodegenerative diseases,diabetes,and cancer.This review focuses on established antioxidant and anti-inflammatory properties of tea polyphenols and underlying mechanisms of their involvement in inflammatory bowel diseases(IBD).Tea polyphenols act as efficient antioxidants by inducing an endogenous antioxidant defense system and maintaining intracellular redox homeostasis.Tea polyphenols also regulate signaling pathways such as nuclear factor-κB,activator protein 1,signal transducer and activator of transcriptions,and nuclear factor E2-related factor 2,which are associated with IBD development.Accumulating pieces of evidence have indicated that tea polyphenols enhance epithelial barrier function and improve gut microbial dysbiosis,contributing to the management of inflammatory colitis.Therefore,this study suggests that supplementation of tea polyphenols could prevent inflammatory conditions and improve the outcome of patients with IBD.展开更多
The gastrointestinal tract of livestock and poultry is prone to challenge by feedborne antigens,pathogens,and other stress factors in the farm environment.Excessive physiological inflammation and oxidative stress that...The gastrointestinal tract of livestock and poultry is prone to challenge by feedborne antigens,pathogens,and other stress factors in the farm environment.Excessive physiological inflammation and oxidative stress that arises firstly disrupts the intestinal epithelial barrier followed by other components of the gastrointestinal tract.In the present review,the interrelationship between intestinal barrier inflammation and oxidative stress that contributes to the pathogenesis of inflammatory bowel disease was described.Further,the role of naturally existing immunomodulatory nutrients such as the omega-3 polyunsaturated fatty acids,citrus pectin,and milk-derived exosomes in preventing intestinal barrier inflammation was discussed.Based on the existing evidence,the possible molecular mechanism of these bioactive nutrients in the intestinal barrier was outlined for application in animal diets.展开更多
Although gastroesophageal reflux disease(GERD),a common chronic disease in clinical practice,has been widely studied,its potential adverse impact on patients is still a significant clinical concern.It is necessary to ...Although gastroesophageal reflux disease(GERD),a common chronic disease in clinical practice,has been widely studied,its potential adverse impact on patients is still a significant clinical concern.It is necessary to understand the pathogenesis of the disease and choose appropriate treatment according to its mechanism.The pathogenesis of GERD is diverse and complex.As the traditional treatment methods are expensive and ineffective in alleviating symptoms in some patients,new treatment options need to be explored.Our previous study suggested that the activation of nuclear factor-kappa beta(NF-κB)in esophageal mucosa may be related to the injury of epithelial barrier function caused by reflux.Based on the literature and our previous study results,it is speculated that inhibition of NF-κB activation may block the insult of GERD on the esophageal mucosal barrier.NF-κB may play an important role in the development of GERD.This article reviews the pathogenesis of GERD and the relationship between NF-κB and GERD,in order to provide new strategies for the treatment of GERD.展开更多
AIM:To investigate the effects of the chemokine stromal cell-derived factor-1(CXCL12) receptor(CXCR4) antagonist AMD3100 on colonic inflammation and epithelial barrier in dextran sulfate sodium(DSS)-induced colitis in...AIM:To investigate the effects of the chemokine stromal cell-derived factor-1(CXCL12) receptor(CXCR4) antagonist AMD3100 on colonic inflammation and epithelial barrier in dextran sulfate sodium(DSS)-induced colitis in mice.METHODS:Experimental colitis was induced by administration of 5% DSS for 7 d,and assays performed on intestinal segments from the ileocecal valve to the anus.Colonic morphology was examined by hematoxylin and eosin staining.Colonic cytokines were determined by enzyme-linked immunosorbent assay.Myeloperoxidase(MPO) activity(indicator of inflammatory infiltration) was observed spectrophotometrically.Gut permeability was assessed by mucosal-to-serosal clearance of fluorescein isothiocyanate-conjugated dextran 4000(FD4) in everted gut sacs.The apoptosis of colonic epithelium was assessed by Hoechst-33342 staining.To further elucidate the role of CXCR4 in colonic inflammation,we also investigated the effect of AMD3100 on migration and cytokine production of isolated peripheral blood mononuclear cells(PBMCs).RESULTS:DSS-induced colitis was characterized by morphologic changes,as well as increased colonic cytokines,inflammatory infiltration,epithelial apoptosis,and intestinal permeability in mice.In AMD3100-treated mice,epithelial destruction,inflammatory infiltration,and submucosal edema were markedly reduced;colonic tumor necrosis factor-α(TNF-α),interleukin-6(IL-6) and interferon-γ(IFN-γ) levels,as well as MPO activity were significantly decreased.Increased intestinal permeability in DSS-treated mice was signif icantly reduced by AMD3100.The number of apoptotic cells in colitis mice was markedly increased after DSS administration,and decreased when treated with the CXCR4 antagonist AMD3100.In pre-activated PBMCs,CXCL12 stimulation signif icantly increased the migration of PBMCs,and was inhibited by AMD3100.Moderately increased TNF-α,IL-6,and IFN-γ from CXCL12-treated PBMCs were also reduced by AMD3100.CONCLUSION:The CXCR4 antagonist AMD3100 exerts therapeutic effects on experimental colitis by inhibiting colonic inflammation and enhancing epithelial barrier integrity.展开更多
Ulcerative colitis(UC)is an incurable and highly complex digestive disease affecting millions of people worldwide.Compared to the current therapeutic drugs,bioactive peptides are more promising and safe substances as ...Ulcerative colitis(UC)is an incurable and highly complex digestive disease affecting millions of people worldwide.Compared to the current therapeutic drugs,bioactive peptides are more promising and safe substances as functional foods or drugs for the prevention and treatment of UC.The alcohol-soluble components from fermentation broth by fresh wheat germ and apple(AC-WGAF)were found to be effective in UC prevention in dextran sulfate sodium-induced mice in vivo.Herein,4 novel peptides are identifi ed from AC-WGAF by membrane ultrafi ltration,recycling preparative high-performance liquid chromatography,and matrix-assisted laser desorption–ionization time-of-fl ight/time-of-fl ight mass spectrometry,possessing anticolitis activity via using an in vitro model.One of those peptides named T24(PVLGPVRGPFPLL)exhibited the most remarkable anti-colitis activity by preventing tight junction protein loss,maintaining epithelial barrier integrity,and promoting cell proliferation during in vitro and in vivo studies by regulating mitogen-activated protein kinase signaling pathways.Thus,T24 is a promising peptide as a functional food or novel drug for UC prevention and treatment.展开更多
The disruption of epithelial barrier integrity is an important factor in the pathogenesis of various immune disorders. However, the restitution of the compromised barrier functions is difficult. This study investigate...The disruption of epithelial barrier integrity is an important factor in the pathogenesis of various immune disorders. However, the restitution of the compromised barrier functions is difficult. This study investigates the regulation of TWIK-related potassium channel-1 （Trek1） in the restitution of intestinal epithelial barrier functions. The human colon epithelial cell line T84 was cultured in monolayers and used to observe epithelial barrier functions in vitro. An intestinal allergy mouse model was created. Cytokine levels were determined by enzyme-linked immunosorbent assay and western blotting. The results showed that Trek1 deficiency induced T84 monolayer barrier disruption. Allergic responses markedly suppressed the expression of Trek1 in the intestinal epithelia via activating the mitogen-activated protein kinase pathways and increasing the expression of histone deacetylase-1. The inhibition of histone deacetylase-1 by sodium butyrate or the administration of a butyrate-producing probiotic （Clostridium butyricum） restored the intestinal epithelial barrier functions and markedly enhanced the effect of antigen-specific immunotherapy. The data suggest that Trek1 is required for the maintenance of intestinal epithelial barrier integrity. Allergic responses induce an insufficiency of Trek1 expression in the intestinal epithelia. Trek1 expression facilitates the restoration of intestinal epithelial barrier functions in an allergic environment.展开更多
Objective To investigate the mechanism of Tojapride,a Chinese herbal formula extract,on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis(RE).Methods Ten out of 85 SD rats wer...Objective To investigate the mechanism of Tojapride,a Chinese herbal formula extract,on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis(RE).Methods Ten out of 85 SD rats were randomly selected as the sham group(n10),and 75 rats were developed a reflux esophagitis model(RE)by the esophageal and duodenal side-to-side anastomosis.Fifty successful modeling rats were divided into different medicated groups through a random number table including the model,low-,medium-,and high-dose of Tojapride as well as omeprazole groups(n10).Three doses of Tojapride[5.73,11.46,22.92 g/(kg•d)]and omeprazole[4.17 mg/(kg•d)]were administrated intragastrically twice daily for 3 weeks.And the rats in the sham and model groups were administered 10 mL/kg distilled water.Gastric fluid was collected and the supernatant was kept to measure for volume,pH value and acidity.Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin(HE)staining,and esophageal epithelial ultrastructure was observed by transmission electron microscopy.The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65(NF-KBp65),κB kinase beta(IKKß),occludin,and zonula occludens-1(ZO-1)in the esophageal tissues were measured by immunohistochemistry and Western blot,respectively.Results The gastric pH value in the model group was significantly lower than the sham group(P<0.05).Compared with the model group,gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher(P<0.05).A large area of ulceration was found on the esophageal mucosa from the model rats,while varying degrees of congestion and partially visible erosion was observed in the remaining groups.Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment.Compared with the sham group,the IKKßlevels were significantly higher in the model group(P<0.05).However,the IKKßlevels were down-regulated after treatment by all doses of Tojapride(P<0.01 or P<0.05).The occluding and ZO-1 levels decreased in the model group compared with the sham group(Ps0.01 or Ps0.05),while both indices were significantly up-regulated in the Tojapride-treated groups(P<0.01 or P<0.05).Conclusions Tojapride could improve the pathological conditions of esophageal epithelium in RE rats.The underlying mechanisms may involve in down-regulating the IKKßexpression and elevating ZO-1 and occludin expression,thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.展开更多
基金supported by the National Natural Science Foundation of China(32001685)the Guidance Plan of Liaoning Natural Science Foundation(20180550776)the Research Initiation Fund of Shenyang Agricultural University(880418026).
文摘Scope:High-fat diet(HFD)induces imbalance in the small intestine environment,where fat digestion and absorption mainly take place.This study aimed to elucidate the mechanisms by which Lonicera caerulea polyphenols(LCP)might inhibit fat absorption,from the perspective of small intestine microbiota and epithelial barrier integrity.Methods and results:Male Sprague-Dawley rats were given HFD with or without co-administration of LCP for 8 weeks.The results showed that LCP supplementation significantly decreased the levels of serum triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C),and increased the contents of fecal sterols,in HFD rats.LCP also inhibited the dysfunction of the small intestine epithelial barrier,via alleviating the oxidative stress activated by Nrf2-ARE pathway,and by modulating the expressions of pro-inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),cyclooxygenase-2(COX-2),nuclear factor kappa-B p65(NF-κB p65)and inducible nitric oxide synthase(iNOS)in the small intestine.Additionally,LCP administration restored the balance in small intestine microbiota and increased the abundance of the specific bacteria,such as Lactobacillus,involved in fat absorption.Conclusion:Our results demonstrated that LCP may be beneficial to inhibit fat absorption.The mechanism seems to be associated with the protection of the epithelial barrier integrity and the modulation of specific bacteria in the small intestine.
基金BK acknowledges the TUBITAK 2210-C National Graduate Scholarship Program and access to the laboratory of Prof.Dr.Sinan Akgol at Biochemistry Department of Ege UniversityThis work was supported by the Presidency of the Republic of Türkiye Strategy Budget Department(2019K12-149080).
文摘The plausibility of human exposure to particulate matter(PM)has witnessed an increase within the last several years.PM of different sizes has been discovered in the atmosphere given the role of dust transport in weather and climate composition.As a regulator,the lung epithelium orchestrates the innate response to local damage.Herein,we developed a lung epithelium-ona-chip platform consisting of easily moldable polydimethylsiloxane layers along with a thin,flexible,and transparent ionic liquid-based poly(hydroxyethyl)methacrylate gel membrane.The epithelium was formed through the culture of human lung epithelial cells(Calu-3)on this membrane.The mechanical stress at the air–liquid interface during inhalation/exhalation was recapitulated using an Arduino-based servo motor system,which applied a uniaxial tensile strength from the two sides of the chip with 10%strain and a frequency of 0.2 Hz.Subsequently,the administration of silica nanoparticles(PM0.5)with an average size of 463 nm to the on-chip platform under static,dynamic,and dynamic+mechanical stress(DMS)conditions demonstrated the effect of environmental pollutants on lung epithelium.The viability and release of lactate dehydrogenase were determined along with proinflammatory response through the quantification of tumor necrosis factor-α,which indicated alterations in the epithelium.
基金Supported by National Natural Science Foundation of China,No. 30772831National Basic Research Program of China, 973program, No. 2009CB522900Shanghai Leading Discipline Project, No. S30304
文摘AIM: To investigate the effects of moxibustion on down-regulation of the colonic epithelial cell apoptosis and repair of the tight junctions in rats with Crohn's disease (CD). METHODS: Sixty male Sprague-Dawley rats were randomly divided into a normal control (NC) group, a model control (MC) group, an herbs-partitioned moxibustion (HPM) group, a mild-warm moxibustion (MWM) group and a salicylazosulphapyridine (SASP) group, with 12 rats in each group. The CD model rats were treated with trinitrobenzene sulphonic acid to induce intestinal inflammation. The rats in the HPM and MWM groups were treated at the Tianshu (ST25) and Qihai (CV6) acupoints once daily for 14 d, and the SASP group was fed SASP twice daily for 14 d. No additional treatment was given to the MC and NC groups. Themicrostructure of the colonic epithelium was observed under a transmission electron microscope, the transepithelial resistance was measured using a shortcircuit current, colonic epithelial cell apoptosis was determined by terminal deoxynucleotidyl transferasemediated dUTP-biotin nick end labelling assay, and the expression of occludin, claudin-1 and zonula occludens-l (ZO-1) in the colonic epithelial junction was determined by Western blotting and immunofluorescence staining. RESULTS: Compared with the MC group, the microstructure of the colonic epithelial barrier was signifi-cantly improved in rats treated with HPM, MWM or SASP, meanwhile, the current flow was reduced signifi-cantly, with values of 168.20 ± 6.14 vs 99.70 ± 3.13, 99.10 ± 4.28 and 120.30 ± 3.65 mA, respectively (P = 0.001). However, the HPM and MWM groups had higher current flow rates than the SASP group (99.70 ± 3.13, 99.10 ± 4.28 vs 120.30 ± 3.65 mA, P = 0.001). The number of the apoptotic colonic epithelial cells in HPM, MWM and SASP groups was largely reduced (61.5 ± 16.91 vs 15.5 ± 8.89, 14.8 ± 6.27 and 24.7 ± 9.68, respectively (P = 0.001); and the expression of occlu- din, claudin-1 and ZO-1 in the MWM and HPM groups was signifi cantly enhanced (0.48 ± 0.10, 0.64 ± 0.09 vs 0.18 ± 0.05 for occludin, 0.12 ± 0.02, 0.17 ± 0.03 vs 0.05 ± 0.01 for claudin-1, and 0.08 ± 0.01, 0.11 ± 0.01 vs 0.02 ± 0.01 for ZO-1). And in SASP group, the expression of occludin and ZO-1 was also signifi cantly increased (0.27 ± 0.04 vs 0.18 ± 0.05 for occludin and 0.05 ± 0.01 vs 0.02 ± 0.01 for ZO-1), but there was no significant difference for claudin-1. The HPM and MWM groups had higher expression of occludin, claudin-1 and ZO-1 than the SASP group. CONCLUSION: HPM and MWM treatment can down-regulate apoptosis of colonic epithelial cells, repair tight junctions and enhance colonic epithelial barrier function in rats with CD.
文摘Irritable bowel syndrome(IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to contribute to the genesis of symptoms in IBS, a search for an underlying aetiology has, to date, proven unsuccessful. Recently, attention has been focused on the microbiota as a possible factor in the pathogenesis of IBS. Prompted by a number of clinical observations, such as the recognition of the de novo development of IBS following enteric infections, as well as descriptions of changes in colonic bacterial populations in IBS and supported by clinical responses to interventions, such as antibiotics and probiotics, that modify the microbiota, various approaches have been taken to investigating the microbiota-host response in IBS, as well as in animal models thereof. From such studies a considerable body of evidence has accumulated to indicate the activation or upregulation of both factors involved in bacterial engagement with the host as well host defence mechanisms against bacteria. Alterations in gut barrier function, occurring in response, or in parallel, to changes in the microbiota, have also been widely described and can be seen to play a pivotal role in generating and sustaining host immune responses both within and beyond the gut. In this manner a plausible hypothesis, based on an altered microbiota and/or an aberrant host response, for the pathogenesis, of at least some instances of IBS, can be generated.
基金Supported by grant No. 0520050040 from the Seoul National University Hospital Research Fund and by KT&G Reserach Fund
文摘AIM： To determine whether Lactobacillus plantarum can modify the deleterious effects of tumor necrosis factor-α （TNF-α） on intestinal epithelial cells. METHODS： Caco-2 cells were incubated with TNF-α alone or in the presence of L. plantarum. Transepithelial electrical resistance was used to measure epithelial barrier function. Interleukin 8 （IL-8） secretion by intestinal epithelial cells was measured using an ELISA. Cellular lysate proteins were immunoblotted using the anti-extracellular regulated kinase （ERK）, anti-phospho- ERK and anti-IκB-α. RESULTS： A TNF-α-induced decrease in transepithelial electrical resistance was inhibited by L. plantarum. TNF- α-induced IL-8 secretion was reduced by L. plantarum. L. plantarum inhibited the activation of ERK and the degradation of IκB-α in TNF-a-treated Caco-2 cells. CONCLUSION： Induction of epithelial barrier dysfunction and IL-8 secretion by TNF-α is inhibited byL. plantarum. Probiotics may preserve epithelial barrier function and inhibit the inflammatory response by altering the signal transduction pathway.
基金Supported by National Natural Science Foundation of China, No. 30500688
文摘AIM: To investigate the effect of emodin on expression of claudin4, claudin5 and occludin, as well as the alveolar epithelial barrier in rats with pancreatitis induced by sodium taurocholate. METHODS: Experimental pancreatitis was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Emodin was injected via the external jugular vein 3 h after induction of acute pancreatitis. Rats from sham operation group and acute pancreatitis group were injected with normal saline (an equivalent volume as emodin) at the same time point. Samples of lung and serum were obtained 6 h after drug administration. Pulmonary morphology was examined with HE staining. Pulmonary edema was estimated by measuring water content in lung tissue samples. Tumor necrosis factorα (TNFα) and interleukin6 (IL6) level were measured by enzymelinked immunospecific assay. Serum amylase and pulmonary myeloperoxidase (MPO) activity were detected by spectrophotometry. Alveolar epithelial barrier was assessed by pulmonary dye extravasation. Expression of claudin4, claudin5 and occludin in lung tissue samples was examined by immunohistology, quantitative realtime reverse transcription polymerase chain reaction and Western blotting analysis, respectively.RESULTS: Pancreatitis-associated lung injury was char-acterized by pulmonary edema, leukocyte infiltration, alveolar collapse, and elevated serum amylase level. The pulmonary damage, pulmonary pathological scores, serum amylase and MPO activity, TNF-α and IL-6 levels, and wet/dry ratio were decreased in rats after treatment with emodin. Immunostaining of claudin-4, claudin-5 and occludin was detected in lung tissue samples from rats in sham operation group, which was distributed in alveolar epithelium, vascular endothelium, and bron-chial epithelium, respectively. The mRNA and protein expression levels of claudin-4, claudin-5 and occludin in lung tissue samples were markedly decreased, the expression level of claudin-4, claudin-5 and occluding was increased, and the pulmonary dye extravasation was reduced in lung tissue samples from rats with acute pancreatitis after treatment with emodin.CONCLUSION: Emodin attenuates pulmonary edema and inflammation, enhances alveolar epithelial barrier function, and promotes expression of claudin-4, claudin-5 and occludin in lung tissue samples from rats with acute pancreatitis.
文摘The pathogenesis of inflammatory bowel diseases (IBDs) seems to involve a primary defect in one or more of the elements responsible for the maintenance of intestinal homeostasis and oral tolerance. The most important element is represented by the intestinal barrier, a complex system formed mostly by intestinal epithelial cells (IECs). IECs have an active role in producing mucus and regulating its composition; they provide a physical barrier capable of controlling antigen traff ic through the intestinal mucosa. At the same time, they are able to play the role of non-professional antigen presenting cells, by processing and presenting antigens directly to the cells of the intestinal immune system. On the other hand, immune cells regulate epithelial growth and differentiation, producing a continuous bi-directional cross-talk within the barrier. Several alterations of the barrier function have been identif ied in IBD, starting from mucus features up to its components, from epithelial junctions up to the Toll-like receptors, and altered immune responses. It remains to be understood whether these defects are primary causes of epithelial damage or secondary effects. We review the possible role of the epithelial barrier and particularly describe the role of IECs in the pathogenesis of IBD.
基金the Scientific Research Foundation of HealthDepartment of Hebei Province,No.20160483
文摘AIM To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis. METHODS Thirty C57BL/6 mice were given either regular drinking water (control group) or 2% (w/v) DSS drinking water (model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 mu g/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-a (TNF-alpha), interleukin 17 (IL-17) and interferon-. (IFN-gamma). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeled-dextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction (TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The mRNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-qPCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-alpha, IL-17 and IFN-gamma. CONCLUSION Our study suggested that poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses, which may shed light on the therapeutic potential of poly I:C in human colitis.
基金supported by Prince of Songkla University(grant number SCI6202058S)Thailand Education Hub-ASEAN Countries(TEH-AC)scholarship(grant number TEH AC 012/2017)Prince of Songkla University,Songkhla,Thailand.
文摘Objective:To investigate the effect of Gracilaria fisheri oligosaccharides(GFO)on inflammation and colonic epithelial barrier dysfunction in colitis mice.Methods:The animals were treated by oral gavage with distilled water,1000 mg/kg inulin,100,500,or 1000 mg/kg GFO for 14 d,or treated with 50 mg/kg mesalamine for 5 d after colitis induction(on day 10).Histopathology,inflammatory cytokines,colonic permeability,and tight junction proteins were investigated by hematoxylin and eosin staining,immunohistochemical staining,Ussing chamber technique,and Western blotting assays,respectively.Results:GFO ameliorated histological damage in colitis mice when compared to untreated colitis mice.Treatments with 100,500,and 1000 mg/kg GFO reduced TNF-αexpression,while IL-1βwas significantly reduced in colitis mice treated with 500 and 1000 mg/kg.Compared to untreated colitis mice,GFO increased transepithelial electrical resistance,reduced fluorescein isothiocyanate-dextran paracellular flux,and modulated tight junction proteins(occludin and claudin 2)in colitis mice.Conclusions:GFO has anti-inflammatory activity and could modulate colonic epithelial barrier dysfunction in acetic acid-induced colitis mice.Furthermore,GFO could modulate the expression of tight junction proteins that play important roles in colonic barrier function.
基金The National Natural Science Foundation of China (32060768)Central guidance for local scientifc and technological development funding projects of China (20231zdf03083)the China Agriculture Research System of MOF and MARA (CARS-37)provided financial support for this study.
文摘Pogostemon cablin essential oil(PEO),extracted from P.cablin,has anti-oxidant,anti-inflammatory,and anti-stress properties,as well as the ability to improve gastrointestinal digestion.This study aims to evaluate the effects of PEO on the performance,rumen epithelial morphology,and barrier function in heat-stressed beef cattle.Thirty-six male Jingjiang cattle at 18 months old were randomly assigned into four groups and fed a diet containing PEO at 0(control),50,100,or 150 mg/kg in the feed concentrate(n=9).All experimental cattle were fed under high temperature and humidity in summer for 60 days.The results indicated that 50 mg/kg of PEO treatment enhanced the average daily gain of beef cattle compared with the control group(P=0.032).All PEO treatments reduced the diamine oxidase activity(P=0.004)and malondialdehyde content(P=0.008)in serum.In addition,the content of 70 kDa heat shock protein in the 100 mg/kg group was increased,and the activity of glutathione peroxidase and total antioxidant capacity in both 100 mg/kg and 150 mg/kg groups were enhanced compared to the control group(P<0.05).More importantly,PEO treatment with 50 mg/kg enhanced the mRNA relative expressions of occludin in ruminal epithelia but decreased the mRNA relative expressions of c-Jun N-terminal kinase,P38 mitogen-activated protein kinases,caspase-3,Beclin1(P<0.05),and extremely significant declined the mRNA relative expressions of extracellular regulated protein kinases and ubiquitin-binding protein in contrast to the control group(P<0.01).These findings indicated that dietary PEO supplementation might be favorable to improve growth performance and repairing damaged rumen epithelium of heat-stressed cattle by down-regulating the mitogen-activated protein kinase signaling pathway.
基金supported by grants from The National Natural Science Foundation of China(No.31971089)the General Project of Chongqing Natural Science Foundation(China)(No.CSTB2022NSCQ-MSX0107)the Scientific Research Innovation Project for Postgraduates in Chongqing City(China)(No.CYS19198).
文摘Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier function.Short-chain fatty acids (SCFAs),as metabolites of the gut microbiota,protect the physiological intestinal barrier;however,they are compromised when VA is deficient.Thus,there is an urgent need to understand how and which SCFAs modulate colonic epithelial barrier integrity in VA deficiency (VAD).Herein,compared with normal VA rats (VAN),at the beginning of pregnancy,we confirmed that the colonic desmosome junction was impaired in the VAD group,and the amounts of acetate,propionate,and butyrate declined because of the decreased abundance of SCFA-producing bacteria (Romboutsia ,Collinsella ,and Allobaculum ).The differentially expressed genes correlated with the gut barrier and the histone deacetylase complex between the VAD and VAN groups were enriched by RNA sequencing.In the VAD group,the expression levels of colonic CEA cell adhesion molecule 1 (CEACAM1) were down-regulated,and the levels of histone deacetylase 1 (HDAC1) and HDAC3 were up-regulated.Intriguingly,the above changes in the VAD groups were rescued by VA supplementation in the early postnatal period.Further study indicated that in Caco-2 cells,butyrate treatment significantly repressed the enrichment of HDAC3 on the promoter of the CEACAM1 gene to induce its expression.Our findings support that butyrate intervention can alleviate the impairment of colonic barrier function caused by VAD,and timely postnatal VA intervention may reverse the damage caused by VAD on gut barrier integrity during pregnancy.
基金supported by the National Natural Science Foundation of China(grant no.81774449).
文摘Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are interdependent and establish a complex interaction network that restricts each other.According to the impact on the human body,there are three categories of symbiotic bacteria,opportunistic pathogens,and pathogenic bacteria.The intestinal microecology participates in digestion and absorption,and material metabolism,and inhibits the growth of pathogenic microorganisms.It also acts as the body’s natural immune barrier,regulates the innate immunity of the intestine,controls the mucosal barrier function,and also participates in the intestinal epithelial cells’physiological activities such as hyperplasia or apoptosis.When the steady-state balance of the intestinal microecology is disturbed,the existing core intestinal microbiota network changes and leads to obesity,diabetes,and many other diseases,especially irritable bowel syndrome,inflammatory bowel disease(IBD),and colorectal malignancy.Intestinal diseases,including tumors,are particularly closely related to intestinal microecology.This article systematically discusses the research progress on the relationship between IBD and intestinal microecology from the pathogenesis,treatment methods of IBD,and the changes in intestinal microbiota.
基金Supported by PiLeJe,37,quai-de-Grenelle,batiment Pollux,75738 Paris cedex 15
文摘AIM: To investigate the effect of the probiotic combination Lactibiane Tolerance<sup>®</sup> (LT) on epithelial barrier function in vitro and in vivo.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.NRF-2020R1F1A1073595 and 2021R1A2C2006745)。
文摘Polyphenols,including phenolic acids,flavonoids,and procyanidins,are abundant in food and beverage derived from plants.Tea(Camellia sinensis)is particularly rich in polyphenols(e.g.,catechins,theaflavins,thearubigins,gallic acid,and flavonols),which are thought to contribute to the health benefits of tea.High intake of tea polyphenols has been described to prevent and/or attenuate a variety of chronic pathological conditions like cardiovascular diseases,neurodegenerative diseases,diabetes,and cancer.This review focuses on established antioxidant and anti-inflammatory properties of tea polyphenols and underlying mechanisms of their involvement in inflammatory bowel diseases(IBD).Tea polyphenols act as efficient antioxidants by inducing an endogenous antioxidant defense system and maintaining intracellular redox homeostasis.Tea polyphenols also regulate signaling pathways such as nuclear factor-κB,activator protein 1,signal transducer and activator of transcriptions,and nuclear factor E2-related factor 2,which are associated with IBD development.Accumulating pieces of evidence have indicated that tea polyphenols enhance epithelial barrier function and improve gut microbial dysbiosis,contributing to the management of inflammatory colitis.Therefore,this study suggests that supplementation of tea polyphenols could prevent inflammatory conditions and improve the outcome of patients with IBD.
基金a European Joint Doctorate Degree programme in Molecular Animal Nutrition(MANNA)between University of Milan(Italy)and University of Veterinary Medicine and Pharmacy in Kosice(Slovakia)funding from the European Union’s Horizon 2020 programme under the Marie Slodowska-Curie Grant agreement No 765423.
文摘The gastrointestinal tract of livestock and poultry is prone to challenge by feedborne antigens,pathogens,and other stress factors in the farm environment.Excessive physiological inflammation and oxidative stress that arises firstly disrupts the intestinal epithelial barrier followed by other components of the gastrointestinal tract.In the present review,the interrelationship between intestinal barrier inflammation and oxidative stress that contributes to the pathogenesis of inflammatory bowel disease was described.Further,the role of naturally existing immunomodulatory nutrients such as the omega-3 polyunsaturated fatty acids,citrus pectin,and milk-derived exosomes in preventing intestinal barrier inflammation was discussed.Based on the existing evidence,the possible molecular mechanism of these bioactive nutrients in the intestinal barrier was outlined for application in animal diets.
文摘Although gastroesophageal reflux disease(GERD),a common chronic disease in clinical practice,has been widely studied,its potential adverse impact on patients is still a significant clinical concern.It is necessary to understand the pathogenesis of the disease and choose appropriate treatment according to its mechanism.The pathogenesis of GERD is diverse and complex.As the traditional treatment methods are expensive and ineffective in alleviating symptoms in some patients,new treatment options need to be explored.Our previous study suggested that the activation of nuclear factor-kappa beta(NF-κB)in esophageal mucosa may be related to the injury of epithelial barrier function caused by reflux.Based on the literature and our previous study results,it is speculated that inhibition of NF-κB activation may block the insult of GERD on the esophageal mucosal barrier.NF-κB may play an important role in the development of GERD.This article reviews the pathogenesis of GERD and the relationship between NF-κB and GERD,in order to provide new strategies for the treatment of GERD.
基金Supported by The Postdoctoral Science Foundation of China, No 20090451573Postdoctoral Science Foundation of Jiangsu Province, No 0902061C
文摘AIM:To investigate the effects of the chemokine stromal cell-derived factor-1(CXCL12) receptor(CXCR4) antagonist AMD3100 on colonic inflammation and epithelial barrier in dextran sulfate sodium(DSS)-induced colitis in mice.METHODS:Experimental colitis was induced by administration of 5% DSS for 7 d,and assays performed on intestinal segments from the ileocecal valve to the anus.Colonic morphology was examined by hematoxylin and eosin staining.Colonic cytokines were determined by enzyme-linked immunosorbent assay.Myeloperoxidase(MPO) activity(indicator of inflammatory infiltration) was observed spectrophotometrically.Gut permeability was assessed by mucosal-to-serosal clearance of fluorescein isothiocyanate-conjugated dextran 4000(FD4) in everted gut sacs.The apoptosis of colonic epithelium was assessed by Hoechst-33342 staining.To further elucidate the role of CXCR4 in colonic inflammation,we also investigated the effect of AMD3100 on migration and cytokine production of isolated peripheral blood mononuclear cells(PBMCs).RESULTS:DSS-induced colitis was characterized by morphologic changes,as well as increased colonic cytokines,inflammatory infiltration,epithelial apoptosis,and intestinal permeability in mice.In AMD3100-treated mice,epithelial destruction,inflammatory infiltration,and submucosal edema were markedly reduced;colonic tumor necrosis factor-α(TNF-α),interleukin-6(IL-6) and interferon-γ(IFN-γ) levels,as well as MPO activity were significantly decreased.Increased intestinal permeability in DSS-treated mice was signif icantly reduced by AMD3100.The number of apoptotic cells in colitis mice was markedly increased after DSS administration,and decreased when treated with the CXCR4 antagonist AMD3100.In pre-activated PBMCs,CXCL12 stimulation signif icantly increased the migration of PBMCs,and was inhibited by AMD3100.Moderately increased TNF-α,IL-6,and IFN-γ from CXCL12-treated PBMCs were also reduced by AMD3100.CONCLUSION:The CXCR4 antagonist AMD3100 exerts therapeutic effects on experimental colitis by inhibiting colonic inflammation and enhancing epithelial barrier integrity.
基金supported by the National Key Research and Development Plan,China(2016YFD0400203-4)the Shenzhen Science and Technology Innovation Commission(KCXFZ20201221173207022)。
文摘Ulcerative colitis(UC)is an incurable and highly complex digestive disease affecting millions of people worldwide.Compared to the current therapeutic drugs,bioactive peptides are more promising and safe substances as functional foods or drugs for the prevention and treatment of UC.The alcohol-soluble components from fermentation broth by fresh wheat germ and apple(AC-WGAF)were found to be effective in UC prevention in dextran sulfate sodium-induced mice in vivo.Herein,4 novel peptides are identifi ed from AC-WGAF by membrane ultrafi ltration,recycling preparative high-performance liquid chromatography,and matrix-assisted laser desorption–ionization time-of-fl ight/time-of-fl ight mass spectrometry,possessing anticolitis activity via using an in vitro model.One of those peptides named T24(PVLGPVRGPFPLL)exhibited the most remarkable anti-colitis activity by preventing tight junction protein loss,maintaining epithelial barrier integrity,and promoting cell proliferation during in vitro and in vivo studies by regulating mitogen-activated protein kinase signaling pathways.Thus,T24 is a promising peptide as a functional food or novel drug for UC prevention and treatment.
文摘The disruption of epithelial barrier integrity is an important factor in the pathogenesis of various immune disorders. However, the restitution of the compromised barrier functions is difficult. This study investigates the regulation of TWIK-related potassium channel-1 （Trek1） in the restitution of intestinal epithelial barrier functions. The human colon epithelial cell line T84 was cultured in monolayers and used to observe epithelial barrier functions in vitro. An intestinal allergy mouse model was created. Cytokine levels were determined by enzyme-linked immunosorbent assay and western blotting. The results showed that Trek1 deficiency induced T84 monolayer barrier disruption. Allergic responses markedly suppressed the expression of Trek1 in the intestinal epithelia via activating the mitogen-activated protein kinase pathways and increasing the expression of histone deacetylase-1. The inhibition of histone deacetylase-1 by sodium butyrate or the administration of a butyrate-producing probiotic （Clostridium butyricum） restored the intestinal epithelial barrier functions and markedly enhanced the effect of antigen-specific immunotherapy. The data suggest that Trek1 is required for the maintenance of intestinal epithelial barrier integrity. Allergic responses induce an insufficiency of Trek1 expression in the intestinal epithelia. Trek1 expression facilitates the restoration of intestinal epithelial barrier functions in an allergic environment.
基金Supported by Natural Science Foundation of China(No.81503560)“Ten Diseases and Ten Drugs”Program and the Cultivation Research of Biological Medicine and Life Science Innovation of Beijing Municipal Science and Technology Commission(No.Z141100002214012,Z161100000116046)。
文摘Objective To investigate the mechanism of Tojapride,a Chinese herbal formula extract,on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis(RE).Methods Ten out of 85 SD rats were randomly selected as the sham group(n10),and 75 rats were developed a reflux esophagitis model(RE)by the esophageal and duodenal side-to-side anastomosis.Fifty successful modeling rats were divided into different medicated groups through a random number table including the model,low-,medium-,and high-dose of Tojapride as well as omeprazole groups(n10).Three doses of Tojapride[5.73,11.46,22.92 g/(kg•d)]and omeprazole[4.17 mg/(kg•d)]were administrated intragastrically twice daily for 3 weeks.And the rats in the sham and model groups were administered 10 mL/kg distilled water.Gastric fluid was collected and the supernatant was kept to measure for volume,pH value and acidity.Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin(HE)staining,and esophageal epithelial ultrastructure was observed by transmission electron microscopy.The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65(NF-KBp65),κB kinase beta(IKKß),occludin,and zonula occludens-1(ZO-1)in the esophageal tissues were measured by immunohistochemistry and Western blot,respectively.Results The gastric pH value in the model group was significantly lower than the sham group(P<0.05).Compared with the model group,gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher(P<0.05).A large area of ulceration was found on the esophageal mucosa from the model rats,while varying degrees of congestion and partially visible erosion was observed in the remaining groups.Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment.Compared with the sham group,the IKKßlevels were significantly higher in the model group(P<0.05).However,the IKKßlevels were down-regulated after treatment by all doses of Tojapride(P<0.01 or P<0.05).The occluding and ZO-1 levels decreased in the model group compared with the sham group(Ps0.01 or Ps0.05),while both indices were significantly up-regulated in the Tojapride-treated groups(P<0.01 or P<0.05).Conclusions Tojapride could improve the pathological conditions of esophageal epithelium in RE rats.The underlying mechanisms may involve in down-regulating the IKKßexpression and elevating ZO-1 and occludin expression,thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.
